Aims: 

The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation (OIC) is the most disabling, since laxatives often fail to provide satisfactory relief. Opioid receptor antagonists with limited systemic bioavailability or a peripherally restricted site of action (peripheral opioid receptor antagonists or PORAs) offer a new opportunity for the specific control of OIC. However, their efficacy and mode of action remains a matter of debate.

Methods: 

The prevalence of OIC and the efficacy of nonspecific and specific treatment options were reviewed. In addition, the mode of action of the available PORAs was analysed.

Results: 

The prevalence of OIC has been reported to vary between 15 and 90%. The specific management of OIC is currently based on 2 drug entities: subcutaneous methylnaltrexone for the reduction of OIC in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the treatment of non-cancer and cancer pain. Both drugs attenuate OIC while the analgesic effect of opioids remains unabated. The efficacy of PORAs in reducing OIC (with an apparent relief in about 50% of patients) is difficult to assess because there is no validated test to differentiate between OIC and non-OIC and because idiopathic constipation increases with age. While the fixed addition of naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate defaecation by provoking an intestinal withdrawal response.

Conclusion: 

The availability of PORAs provides a novel opportunity to specifically control OIC and other peripheral adverse effects of opioid analgesics. The continuous dosing of naloxone in fixed combination with an opioid has the advantage of few side effects, while the intestinal withdrawal effect provoked by methylnaltrexone can be associated with pain and, in very rare cases, bowel perforation.